Cornexistin and hydroxycornexistin are natural products derived from the fungus Paecilomyces divaricatus formerly known as Paecilomyces variotii SANK21086. Both, cornexistin and hydroxycornexistin, are highly potent herbicides that have the unique quality of being harmless to corn plants. Because of this quality, both molecules have attracted research interest. Their interesting nine-membered ring structure contains a maleic anhydride and a key exocyclic ethylidene; this structure also indicates membership in the nonadride family activity and its highly functionalized structure. As part of these discovery efforts, the Sankyo Corporation discovered cornexistin during the screening of biological extracts for herbicidal use (JP2256602). Cornexistin showed good activity as a herbicide as well as relative inactivity towards corn plants. Sankyo's characterization showed this fungal natural product to be a member of the nonadride family, a group of natural products known for their interesting structural characteristics including a central nine-membered ring, fused maleic anhydrides and pendant alkyl chains. Cornexistin and hydroxycornexistin has been synthesized by chemical synthesis only as diastereomeres (Org. Biomol. Chem., 2008, 6, 4012-4025). Nine-membered carbocyclic structures in general are rare in nature and their synthesis as well as the genes involved in the synthesis are still unknown and not described.
Isolation of cornexistin from the cultures of Paecilomyces species originally identified as Paecilomyces variotii SANK21086 was published as early as 1989 by the Sankyo research group JP2256602). Later work from the DOW Elanco group described identification of hydroxycornexistin also produced in Paecilomyces variotii SANK 21086 (U.S. Pat. No. 5,424,78). The yield of the producing strain SANK 21086 in fermentation is believed to be too low for production purposes.
The technical problem underlying the present invention can be seen as the provision of additional means and methods for the production of cornexistin or hydroxycornexistin or for the production of cornexistin and hydroxycornexistin. The technical problem is solved by the embodiments characterized in the claims and herein below.